Abstract In our previous study, a pectin NOP from Gannan navel orange (Citrus sinensis Osbeck cv. Newhall) peels has been gained. This study sequentially determines its structure using methylation analysis and NMR spectroscopy, and evaluates its gastroprotective activity against alcohol-induced gastric mucosal lesions (AGML) in rats. Meanwhile, the mechanism was explored by RNA-seq, western blot, 16S rRNA and untargeted metabolomics analyses along with correlation analyses and molecular docking. Results showed that NOP consisted of HG domain, RG-I domain and β-1,6-D-glucan structure. The side chains of RG-I domain were composed of →5)-α-L-Araf-(1→, β-D-Galp-(1→, →4)-β-D-Galp-(1→ and →3,6)-β-D-Galp-(1→ residues. NOP ameliorated gastric lesion, decreased inflammatory responses and protein expressions of inflammatory signaling pathways-related hub targets (Ccl2, Cxcl1, Icam1, Il6, Jun and Lif), changed gene expressions and metabolism of gastric tissues, and regulated gut microbiota in AGML rats. Moreover, gut microbiota biomarkers, biochemical indexes and differential metabolites affected by NOP showed significantly positive and negative correlations. Furthermore, the representative metabolites like hypoxanthine and the inflammatory signaling pathways-related hub targets exhibited good binding activities. It can be concluded that NOP is a candidate for alleviating AGML, exerting gastroprotection through inflammatory signaling pathways, gut microbiota and metabolites in AGML rats. This study provides theoretical basis for the exploitation and utilization of NOP in preventing AGML, and the future mechanism investigation.
Hao et al. (Mon,) studied this question.